Food contains bioactive compounds that may prevent changes in gut microbiota associated with Westernized diets. The aim of this study is to explore the possible additive effects of d-fagomine and ω-3 PUFAs (EPA/DHA 1:1) on gut microbiota and related risk factors during early stages in the development of fat-induced pre-diabetes. Male Sprague Dawley (SD) rats were fed a standard diet, or a high-fat (HF) diet supplemented with d-fagomine, EPA/DHA 1:1, a combination of both, or neither, for 24 weeks. The variables measured were fasting glucose and glucose tolerance, plasma insulin, liver inflammation, fecal/cecal gut bacterial subgroups and short-chain fatty acids (SCFAs). The animals supplemented with d-fagomine alone and in combination with ω-3 PUFAs accumulated less fat than those in the non-supplemented HF group and those given only ω-3 PUFAs. The combined supplements attenuated the high-fat-induced incipient insulin resistance (IR), and liver inflammation, while increasing the cecal content, the Bacteroidetes:Firmicutes ratio and the populations of Bifidobacteriales. The functional effects of the combination of d-fagomine and EPA/DHA 1:1 against gut dysbiosis and the very early metabolic alterations induced by a high-fat diet are mainly those of d-fagomine complemented by the anti-inflammatory action of ω-3 PUFAs.
Diet-induced obesity has been linked to metabolic disorders such as cardiovascular diseases and type 2 diabetes. A factor linking diet to metabolic disorders is oxidative stress, which can damage biomolecules, especially proteins. The present study was designed to investigate the effect of marine omega-3 polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and their combination with grape seed polyphenols (GSE) on carbonyl-modified proteins from plasma and liver in Wistar Kyoto rats fed an obesogenic diet, namely high-fat and high-sucrose (HFHS) diet. A proteomics approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labelling of protein carbonyls, visualization of FTSC-labelled protein on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Results showed the efficiency of the combination of both bioactive compounds in decreasing the total protein carbonylation induced by HFHS diet in both plasma and liver. The analysis of carbonylated protein targets, also referred to as the ‘carbonylome’, revealed an individual response of liver proteins to supplements and a modulatory effect on specific metabolic pathways and processes due to, at least in part, the control exerted by the supplements on the liver protein carbonylome. This investigation highlights the additive effect of dietary fish oils and grape seed polyphenols in modulating in vivo oxidative damage of proteins induced by the consumption of HFHS diets.
Some functional food components may help maintain homeostasis by promoting balanced gut microbiota. Here, we explore the possible complementary effects of d-fagomine and ω-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA 1:1) on putatively beneficial gut bacterial strains. Male Sprague–Dawley rats were supplemented with d-fagomine, ω-3 PUFAs, or both, for 23 weeks. Bacterial subgroups were evaluated in fecal DNA by quantitative real-time polymerase chain reaction (qRT-PCR) and short-chain fatty acids were determined by gas chromatography. We found that the populations of the genus Prevotella remained stable over time in animals supplemented with d-fagomine, independently of ω-3 PUFA supplementation. Animals in these groups gained less weight than controls and rats given only ω-3 PUFAs. d-Fagomine supplementation together with ω-3 PUFAs maintained the relative populations of Bacteroides. ω-3 PUFAs alone or combined with d-fagomine reduced the amount of acetic acid and total short-chain fatty acids in feces. The plasma levels of pro-inflammatory arachidonic acid derived metabolites, triglycerides and cholesterol were lower in both groups supplemented with ω-3 PUFAs. The d-fagomine and ω-3 PUFAs combination provided the functional benefits of each supplement. Notably, it helped stabilize populations of Prevotella in the rat intestinal tract while reducing weight gain and providing the anti-inflammatory and cardiovascular benefits of ω-3 PUFAs.
Adipose tissue is now recognized as an active organ with an important homeostatic function in glucose and lipid metabolism and the development of insulin resistance. The present research investigates the role of lipid mediators and lipid profiling for controlling inflammation and the metabolic normal function of white adipose tissue from rats suffering from diet-induced prediabetes. Additionally, the contribution to the adipose lipidome induced by the consumption of marine ω-3 PUFAs as potential regulators of inflammation is addressed. For that, the effects on the inflammatory response triggered by high-fat high-sucrose (HFHS) diets were studied in male Sprague-Dawley rats. Using SPE-LC-MS/MS-based metabolo-lipidomics, a range of eicosanoids, docosanoids and specialized pro-resolving mediators (SPMs) were measured in white adipose tissue. The inflammatory response occurring in prediabetic adipose tissue was associated with the decomposition of ARA epoxides to ARA-dihydroxides, the reduction of oxo-derivatives and the formation of prostaglandins (PGs). In an attempt to control the inflammatory response initiated, LOX and non-enzymatic oxidation shifted toward the production of the less pro-inflammatory EPA and DHA metabolites rather than the high pro-inflammatory ARA hydroxides. Additionally, the change in LOX activity induced the production of intermediate hydroxides precursors of SPMs as protectins (PDs), resolvins (Rvs) and maresins (MaRs). This compensatory mechanism to achieve the restoration of tissue homeostasis was significantly strengthened through supplementation with fish oils. Increasing proportions of ω-3 PUFAs in adipose tissue significantly stimulated the formation of DHA-epoxides by cytochrome P450, the production of non-enzymatic EPA-metabolites and prompted the activity of 12LOX. Finally, protectin PDX was significantly reduced in the adipose tissue of prediabetic rats and highly enhanced through ω-3 PUFAs supplementation. Taken together, these actively coordinated modifications constitute key mechanisms to restore adipose tissue homeostasis with an important role of lipid mediators. This compensatory mechanism is reinforced through the supplementation of the diet with fish oils with high and balanced contents of EPA and DHA. The study highlights new insides on the targets for effective treatment of incipient diet-induced diabetes and the mechanism underlying the potential anti-inflammatory action of marine lipids.
D-Fagomine (1,2 dideoxynojirimycin) is an iminosugar, a carbohydrate analogue that includes an endocyclic nitrogen instead of oxygen, that is naturally present in buckwheat and buckwheat-based foodstuffs. This study examines the long-term functional effect of d-fagomine on sucrose-induced factors of metabolic syndrome and explores possible molecular mechanisms behind its action. We evaluated Wistar Kyoto rats fed a standard diet were given a 35% sucrose (glucose/fructose) solution with dfagomine (or not, for comparison) or mineral water (controls) for 24 weeks. The variables measured were body weight and energy intake; glucose tolerance (oral glucose tolerance test); plasma leptin concentration; plasma lipid profile; the populations of Bacteroidetes, Firmicutes, bacteroidales, clostridiales, enterobacteriales, and Escherichia coli in feces; blood pressure; urine uric acid and F 2t isoprostanes (F 2 -IsoPs); perigonadal fat deposition and hepatic histology and diacylglycerols (DAGs) in liver and adipose tissue. We found that d-Fagomine reduced sucrose induced hypertension, urine uric acid, F 2 -IsoPs as markers of oxidative stress (OS), steatosis and liver DAGs (32:1, 32:2, 34:1 and 36:2) without affecting perigonadal (visceral) fat deposition or DAG levels in visceral adipose tissue. It showed a slight tendency to reduce sugar induced impaired glucose tolerance. d-Fagomine also promoted excretion of enterobacteriales generated by the dietary intervention. We postulate that fructose increases visceral fat deposition independently of liver de novo liposynthesis and that d-fagomine attenuates steatosis and blood pressure mainly by reducing liver fructose levels. The reduction of blood pressure may be associated with an effect on uric acid synthesis while the reduced levels of selected active liver DAGs may explain the weak effect on sucrose-induced impaired glucose tolerance, which may be primarily induced by visceral fat deposition. In conclusion, the increased populations of excreted enterobacteriales may be connected to the levels of excreted uric acid. d-Fagomine counteracts sucrose-induced steatosis and hypertension presumably by reducing the postprandial levels of fructose in the liver as a consequence of intestinal sucrase inhibition.
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